Table 15h. Antiretroviral Therapy-Associated Adverse Effects and Management Recommendations—Lipodystrophies and Weight Gain

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Table 15h. Antiretroviral Therapy-Associated Adverse Effects and Management Recommendations—Lipodystrophies and Weight Gain
Adverse Effects Associated ARVs Onset/Clinical Manifestations Estimated Frequency Risk Factors Prevention/Monitoring Management
Lipodystrophy (Fat Maldistribution)
General Information
See below for specific associations. Onset:
  • Increase in trunk and limb fat is the first sign; peripheral fat wasting may not appear for 12–24 months after ART initiation.
Frequency is low (<5%) with current regimens. Genetic predisposition

Puberty

HIV-associated inflammation

Older age

Longer duration of ART

Body habitus
Prevention:
  • Initiate  a calorically appropriate low-fat diet and an exercise regimen.
Monitoring:
  • BMI measurement
  • Waist circumference and waist-hip ratio
Physicians should perform a regimen review and consider changing the regimen when lipodystrophy occurs.

Improvement in fat maldistribution can vary following a regimen change. Improvement may occur after several months or years, or it may not occur at all.
Central Lipohypertrophy
or
Lipo-Accumulation
Can occur in the absence of ART, but these conditions most often are associated with the use of PIs and EFV.  Presentation:
  • Central fat accumulation with increased abdominal girth, which may include a dorsocervical fat pad (buffalo hump). Gynecomastia may occur in males, or breast hypertrophy may occur in females, particularly with the use of EFV.
Frequency is low (<5%) with current regimens. Obesity before initiation of therapy

Sedentary lifestyle
Prevention:
  • Initiate a calorically appropriate low-fat diet and an exercise regimen.
Monitoring:
  • BMI measurement
  • Waist circumference and waist-hip ratio

Counsel patient on lifestyle modification and dietary interventions (e.g., maintaining a calorically appropriate diet that is low in saturated fats and simple carbohydrates and starting an exercise regimen, especially strength training).

Recommend smoking cessation (if applicable) to decrease future CVD risk.

Consider using an INSTI instead of a PI or EFV, although some INSTIs may be associated with generalized weight gain (see below)Consider using an INSTI instead of a PI or EFV, although some INSTIs may be associated with generalized weight gain (see below).

Data are Insufficient to Allow the Panel to Safely Recommend Use of Any of the Following Modalities in Children:

  • Recombinant human growth hormone
  • Growth hormone-releasing hormone
  • Metformin
  • Thiazolidinediones
  • Recombinant human leptin
  • Anabolic steroids
  • Liposuction
Facial/Peripheral Lipoatrophy Most cases are associated with the use of ZDV, a thymidine analogue NRTI. Presentation:
  • Thinning of subcutaneous fat in the face, buttocks, and extremities, measured as a decrease in trunk/limb fat by DXA or triceps skinfold thickness. Preservation of lean body mass distinguishes lipoatrophy from HIV-associated wasting.
Frequency is low (<5%) with current regimens. Underweight before ART initiation Prevention:
  • Limit the use of ZDV.
Monitoring:
  • Patient self-report and physical examination are the most sensitive methods of monitoring lipoatrophy.
Replace ZDV with another NRTI when possible.

Data are Insufficient to Allow the Panel to Safely Recommend Use of Any of the Following Modalities in Children:
  • Injections of poly-L-lactic acid
  • Recombinant human leptin
  • Autologous fat transplantation
  • Thiazolidinediones
Weight Gain Significant weight gain may occur with all ARV regimens, but it appears to be more pronounced with DTG, BIC, and TAF. Gradual weight gain after initiating ARV drugs is common with all currently used regimens. The mechanism for weight gain is unclear and under investigation. Rate of development of obesity is unclear. In Adults:
  • Low pre-treatment BMI
  • Older age
  • Female sex
  • Black race
Risk factors for weight gain have not been evaluated yet in infants and children.
Prevention:
  • Initiate a calorically appropriate low-fat diet and an exercise regimen.
Monitoring:
  • BMI measurement
  • Waist circumference and waist-hip ratio
Counsel patient on lifestyle modification and dietary interventions (e.g., maintaining a calorically appropriate healthy diet that is low in saturated fats and simple carbohydrates and starting an exercise regimen, especially strength training).
Key: ART = antiretroviral therapy; ARV = antiretroviral; BIC = bictegravir; BMI = body mass index; CVD = cardiovascular disease; DTG = dolutegravir; DXA = dual energy x-ray absorptiometry; EFV = efavirenz; INSTI = integrase strand transfer inhibitor; NRTI = nucleoside reverse transcriptase inhibitor; PI = protease inhibitor; TAF = tenofovir alafenamide; ZDV = zidovudine